DESCRIPTION (Verbatim from the Applicant's Abstract): This project will develop novel, widely applicable, non-invasive methods for simultaneous dual-isotope imaging, using single photon emission computed tomography (SPECT). While applicable to diagnostic nuclear medicine procedures in general, our interest is in the simultaneous imaging of two neurotransmitter systems, and the complex interactions between them, leading to improved understanding of several neurological and psychiatric disorders, such as Parkinson's disease, schizophrenia etc. The recent development of Tc-99m labeled dopamine transporter ligands by this group has made possible the simultaneous study of CNS function using compounds labelled with Tc-99m and I-123. However, when these isotopes are imaged simultaneously, the limited energy resolution of the SPECT system, combined with scatter of the photons in the subject, cause significant degradation of image quality, and prevent accurate quantification. Conventional studies for imaging different isotopes in the same subject require a two-scan protocol. However, simultaneous dual-isotope imaging offers significant advantages, providing improved quantification and segmentation of receptors, perfect spatial alignment between images, and elimination of potential confounds due to changes in patient physiology between scans. There are also considerable benefits for patients as they do not have to return for additional scans, leading to significant cost savings. This project proposes a number of novel analysis techniques which utilize the latest SPECT scanner technology, maximizing the amount of available information from each scan, while minimizing any assumptions about the data. The techniques to be investigated are: 1) Model-based iterative reconstruction algorithms, with accurate corrections for energy window cross-talk and scatter derived from Monte Carlo computer simulations. 2) Compartmental kinetic models, incorporating energy window cross-talk into the model. Simultaneous dual isotope studies will be performed, using Tc-99m and I-123 labeled tracers, and the application of these techniques will be compared against the single isotope studies performed under the same conditions in phantoms and non-human primates. Optimization of experimental settings, such as energy windows, will be performed to maximize the available information, while preserving image quality and reducing any bias to a minimum. Ultimately, in a routine clinical setting, these techniques will produce higher quality quantitative and diagnostic results, leading to an increase in our understanding of brain function in a range of neurological and psychiatric disorders.